Siberian Scientists Develop 'Smart Drugs' for Cancer and HIV Based on Nucleic Acids
Specialists at the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (SB RAS), are working on a new class of drugs—therapeutic oligonucleotides. These 'smart' molecules can specifically target mutated RNA, opening up possibilities for treating severe genetic and infectious diseases, including cancer and HIV.
Therapeutic Oligonucleotides: How Siberian Scientists Create 'Smart Drugs' for Cancer and HIV
Introduction
"The core idea is this: once we determine the genetic structure of a pathogen, we can create a construct that will specifically target only the genome of that 'pest.'"
These words from Dmitry Pyshny, Deputy Director of the Institute of Chemical Biology and Fundamental Medicine SB RAS and Doctor of Chemical Sciences, describe the essence of a scientific revolution currently underway in Novosibirsk's Akademgorodok. It's about therapeutic oligonucleotides—synthetic fragments of nucleic acids capable of 'switching' genes on and off, much like the software code of a living organism.
This technology, which Nobel laureate Sidney Altman calls 'the antibiotics of the future,' can treat diseases once considered incurable: oncology, HIV, genetic disorders, and tuberculosis. Today, Russian scientists are on the verge of creating the first domestic drug of this class, developing unique molecules with no global analogs—phosphorylguanidines.
Event Details and Timeline
What Are Therapeutic Oligonucleotides?
Oligonucleotides are short chains of nucleic acids (DNA or RNA) consisting of 13–25 nucleotides. Their 'smart' properties stem from their ability to bind to complementary sequences of messenger RNA (mRNA) in cells, blocking the synthesis of 'abnormal' or excess proteins.
Main classes of therapeutic oligonucleotides:
- Antisense oligonucleotides (ASOs) — bind to target mRNA and inactivate it (nusinersen for SMA)
- Small interfering RNAs (siRNAs) — trigger RNA interference, 'silencing' genes (patisiran for amyloidosis)
- Aptamers — fold into unique 3D structures, binding to target proteins
To date, 24 oligonucleotide drugs have been approved worldwide for 16 clinical indications. In 2025 alone, the FDA approved three new drugs of this class: fitusiran (hemophilia), donidalorsen (hereditary angioedema), and plozasiran (familial chylomicronemia syndrome).
Russian Development: Phosphorylguanidines
The key difference of the Russian development is a completely original chemical modification of oligonucleotides called 'phosphorylguanidines.'
Problem scientists are solving: Natural oligonucleotides, when introduced into the body, encounter defense mechanisms—they are attacked by nucleases (enzymes that destroy foreign DNA/RNA). To reach their target, chemical modifications are needed to 'trick' the body.
"The human body, like others, has a whole arsenal of means to fight foreign nucleic acids," comments Dmitry Pyshny. "So the question is: we need to develop oligonucleotide derivatives that can deceive living systems, reach their target, exert an effect, and be non-toxic."
Advantages of phosphorylguanidines:
- Stability in biological fluids — not degraded by nucleases
- Non-toxicity — no side effects demonstrated in completed trials
- Ease of synthesis — produced on standard automated equipment
- Fully domestic development — intellectual property of Russia
Delivery Systems: How to Send the Drug to the Right Cell
The second key problem solved by scientists at ICBFM SB RAS is targeted delivery. When administered intravenously, oligonucleotides spread throughout the body and are quickly excreted by the kidneys, failing to reach their target.
"There are a number of proteins whose overexpression is associated with cancer, inflammation, and so on," explains Marina Zenkova, Head of the Laboratory of Nucleic Acid Biochemistry at ICBFM SB RAS and Doctor of Biological Sciences. "An antisense nucleotide can suppress their synthesis, and consequently, the spread of infection. The main problem is delivery to the right place."
Developed solution: Scientists use cationic liposomes—particles up to 100 nanometers in size built from lipids. They bind to oligonucleotides, protect them in the blood, and facilitate cell entry.
Personalized delivery for oncology: Liposomes are modified with folic acid because cancer cells overexpress folate receptors on their surface. This ensures targeted interaction specifically with tumor cells. "We are now trying to create even more complex addressing systems, looking for ways to attach peptides and antibodies that can stimulate the uptake of complexes by specific cells," adds Marina Zenkova.
Development Status and Prospects
The work is carried out within the Russian-American Laboratory of Biomedical Chemistry under the leadership of Nobel laureate Sidney Altman.
Current stage: Scientists are approaching in vivo studies, selecting the most promising candidates for preclinical trials.
Targets for intervention:
- Tuberculosis — shown promise against an analog of Koch's bacillus
- Genetic mutations — Duchenne dystrophy, where oligonucleotides correct mRNA maturation
- Oncology — suppression of overexpressed oncoproteins
- HIV — suppression of viral protein synthesis
Immediate plans: Conduct preclinical trials at the institute in collaboration with the Federal Research Center Institute of Cytology and Genetics SB RAS. "We are approaching the end of the project, but not the end of the work. The laboratory will be preserved, and research will continue," emphasizes Dmitry Pyshny.
In July 2026, ICBFM SB RAS will hold the All-Russian Conference 'Engineering Biology and Biopharmaceutics,' where therapeutic nucleic acids, aptamers, RNA and DNA vaccines, and targeted delivery systems will be discussed.
Impact and Significance
For Medical Science: Confirmation of a Global Trend
2025 was a landmark year for global oligonucleotide therapy: with 24 approved drugs, this class of medicines has finally transitioned from experimental to clinically mature. Modern research uses GalNAc conjugation for targeted liver delivery, chemical modifications for nuclease protection, and AI design to improve specificity.
The Russian development of phosphorylguanidines fits into this global trend, offering a fundamentally new chemical solution to the problems of stability and delivery. "Professor Altman himself calls such oligonucleotide-based compounds the antibiotics of the future," notes Dmitry Pyshny.
For Russian Healthcare: Technological Sovereignty
The development of phosphorylguanidines is entirely domestic intellectual property. In an environment where foreign patents block the use of many technologies, creating an own platform for oligonucleotide drugs is of strategic importance.
"The aforementioned derivatives are patented, and we, understanding the principles of their synthesis, could, in good faith, make something similar ourselves, but we have no right to use the platform of others' work because it is not our intellectual property," explains Dmitry Pyshny.
For Oncology: New Horizons
The oncology direction is especially important. "The problem is that the most malignant tumors have few surface receptors—identification marks," states Marina Zenkova. However, the use of folic acid and the prospect of attaching peptides and antibodies open the way to targeted therapy even for aggressive, metastatic tumors.
An additional direction is diagnostics: ICBFM SB RAS scientists are also developing fluorescent nucleic acid derivatives for biosensors that can detect mutations at the patient's bedside without complex PCR equipment.
Reactions of Key Players
The international scientific community confirms the promise of this direction. In a review article published in the journal Molecular Therapy: Nucleic Acids (2025), the authors note: 'Nucleic acids have established themselves as therapeutic agents for targeting both coding and non-coding sequences. Several types of nucleic acid modalities, including siRNA, mRNA, aptamers, and antisense oligonucleotides, have been approved by regulatory agencies for therapeutic use.'
Partners and collaborations: The developers of phosphorylguanidines are in contact with colleagues from Moscow, Sweden, and the UK, providing derivatives for independent analysis. "In tests conducted, so to speak, by other hands, the presence of the specified properties is also confirmed," notes Dmitry Pyshny.
SB RAS and Rostec support the development of this direction. In 2026, a specialized conference on engineering biology and biopharmaceutics will be held in Novosibirsk's Akademgorodok, indicating the high priority of the topic.
Forecast and Conclusions
The development of therapeutic oligonucleotides at ICBFM SB RAS is at a critical stage of transition from fundamental research to preclinical trials.
Near-term prospects (2026–2027):
- Completion of selecting the most promising candidates for in vivo studies
- Start of preclinical trials at the institute and the Federal Research Center Institute of Cytology and Genetics SB RAS
- Expansion of the range of targets—from tuberculosis to oncology and genetic diseases
Long-term challenges (2028–2030):
- Entering clinical trials in humans—the most difficult and expensive stage
- Ensuring scalable production of phosphorylguanidines
- Regulatory approval by the Ministry of Health of the Russian Federation
Main conclusion:
Novosibirsk scientists are creating not just a new drug, but a technological platform for an entire class of 'smart drugs.' Phosphorylguanidines could be Russia's answer to the global trend of oligonucleotide therapy—a trend that is expected to only gain momentum in the coming decades.
As Dmitry Pyshny said: 'We are approaching the end of the project, but not the end of the work.' And in these words lies the key characteristic of the moment: a fundamental breakthrough has already been made, but the path from a laboratory sample to the pharmacy is just beginning. However, the very fact that Russia has its own original platform for creating therapeutic nucleic acids allows us to look to the future with cautious but real optimism.
— Editorial Team
